This invention relates to an inclusion compound holding therein an active component and allowing the active component to be released therefrom slowly and stably over a long time.
As an inclusion compound heretofore known in the art to be useful for a similar purpose, there may be cited a host-guest type inclusion compound which comprises cyclodextrin and an active component. Cyclodextrin is a cyclic oligo-saccharide having at least six D-gluclose units linked in an .alpha.-1,4 structure. This inclusion compound is soluble in water, shows good crystallinity, and possesses an ability to protect and stabilize the active component as its guest against chemical change such as oxidation and photodecomposition. Numerous studies have been made to date with a view to exploiting these advantageous properties of the inclusion compound for solubilizing sparingly soluble substances, divesting volatile substances of volatility to ensure their prolonged preservation, deodorizing offensive smelling substances, converting oily substances into finely divided solids, masking bitter tastes of foodstuffs, and materializing controlled release of aromas from perfumes and physiologically active substances from pharmaceutical compositions.
In fact, in the medicines, agricultural pesticides, perfumes, etc. available today, there are found those which are desired to release their active components steadily for prolonged periods. Inclusion compounds which hold such active components therein as their guest components hold promise of meeting this condition.
When these inclusion compounds are used as medicines, agricultural pesticides, perfumes, etc., however, they more often than not to come into substantial contact with aqueous solutions.
The formation of the inclusion compound with cyclodextrin in an aqueous solution and the dissociation of the inclusion compound into cyclodextrin and the guest component in an aqueous solution are both reactions of equilibrium. The extent to which the dissociation proceeds depends on the dissociation content, Kd, which generally ranges from 0.1 to 0.0001 and the concentrations of the components of the compound. When the inclusion compound in a solid state is dissolved in water, therefore, the dissolved inclusion compound and the guest component liberated from the compound in consequence of the dissociation are diffused and diluted so much as to expedite the dissociation. Thus, it is difficult to control the release of the guest, i.e. the active compound in the solution. This fact constitutes itself the main cause for the difficulty encountered when efforts are made to prepare an inclusion compound of cyclodextrin holding therein an active component such as a medicine, agricultural pesticide, or perfume in the hope of enabling the inclusion compound to retain the active component intact for a long time.
For the solution of this difficulty, it is imperative to curb the diffusion of the inclusion compound and the cyclodextrin component and, at the same time, enable the active component alone to be diffused and released from the inclusion compound. As one measure, the method of enclosing the inclusion compound with a container which is permeable to the guest component and impermeable to the cyclodextrin component is now under study. However, since the average molecular weight of cyclodextrin is about 1000 and that of an active substance is in the range of 100 to 500, it is not possible to obtain a selective membrane which is impervious to cyclodextrin and pervious to the active substance. Thus, the method just described has not yet been perfected.
An object of this invention is to provide an inclusion compound-containing composite which enables the active component held within the inclusion compound to be released steadily from the composite over a long period of time.